Details

Autor(en) / Beteiligte

• Chen, Yiliang
• Kennedy, David J
• Ramakrishnan, Devi Prasadh
• Yang, Moua
• Huang, Wenxin
• Li, Zhichuan
• Xie, Zijian
• Chadwick, Alexandra C
• Sahoo, Daisy
• Silverstein, Roy L

Titel

Oxidized LDL-bound CD36 recruits an Na⁺/K⁺-ATPase-Lyn complex in macrophages that promotes atherosclerosis

Ist Teil von

• Science signaling, 2015-09, Vol.8 (393), p.ra91

Ort / Verlag

United States

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• One characteristic of atherosclerosis is the accumulation of lipid-laden macrophage foam cells in the arterial wall. We have previously shown that the binding of oxidized low-density lipoprotein (oxLDL) to the scavenger receptor CD36 activates the kinase Lyn, initiating a cascade that inhibits macrophage migration and is necessary for foam cell generation. We identified the plasma membrane ion transporter Na(+)/K(+)-ATPase as a key component in the macrophage oxLDL-CD36 signaling axis. Using peritoneal macrophages isolated from Atp1a1 heterozygous or Cd36-null mice, we demonstrated that CD36 recruited an Na(+)/K(+)-ATPase-Lyn complex for Lyn activation in response to oxLDL. Macrophages deficient in the α1 Na(+)/K(+)-ATPase catalytic subunit did not respond to activation of CD36, showing attenuated oxLDL uptake and foam cell formation, and oxLDL failed to inhibit migration of these macrophages. Furthermore, Apoe-null mice, which are a model of atherosclerosis, were protected from diet-induced atherosclerosis by global deletion of a single allele encoding the α1 Na(+)/K(+)-ATPase subunit or reconstitution with macrophages that lacked an allele encoding the α1 Na(+)/K(+)-ATPase subunit. These findings identify Na(+)/K(+)-ATPase as a potential target for preventing or treating atherosclerosis.